Stage-Specific Risk of Recurrence and Death From Melanoma in Denmark, 2008-2021: A National Observational Cohort Study of 25 720 Patients With Stage IA to IV Melanoma.

Importance: To ensure optimal treatment and surveillance of patients with melanoma, knowledge of the clinical stage-specific risk of recurrence, mortality, and recurrence patterns across the American Joint Committee on Cancer Eighth Edition (AJCC8) substages is needed. Objective: To estimate stage-specific recurrence and melanoma-specific mortality rates, assess absolute stage-specific risks of recurrence and mortality, and describe stage-specific recurrence patterns, including conditional rates. Design: Retrospective cohort study of prospectively collected nationwide population-based registry data. Setting: Nationwide, population-based cohort study. Participants: The 25 720 Danish patients, 18 years or older, diagnosed with first-time stage IA to IV cutaneous melanoma between January 1, 2008, and December 31, 2019, were included and followed up from time of primary treatment until December 31, 2021. Exposures: First diagnosis of stage IA to IV cutaneous melanoma. Main Outcomes: Stage-specific cumulative incidence of recurrence and melanoma-specific mortality, melanoma-specific recurrence-free survival, and assessed absolute stage-specific risks of recurrence and melanoma-specific mortality. Secondary outcomes were stage-specific recurrence patterns, including conditional rates, and melanoma-specific survival. Results: We followed up 25 720 patients for a median of 5.9 years (95% CI, 58.9-59.3 years). Mean age was 59.1 years (95% CI, 58.9-59.3 years). Patients with stage IIB to IIC melanoma were older, had more comorbidities at diagnosis, and had the lowest rate of pathologic staging by sentinel node biopsy (81.6%-87.4%). A total of 10.6% of patients developed recurrence; first recurrence included distant recurrence, alone or with synchronous locoregional recurrence, in 56.6% of patients. We found a comparable risk of recurrence in stages IIIA and IIB (29.7% vs 33.2%) and in stages IIIB and IIC (35.9% vs 36.8%), respectively. Melanoma-specific mortality was comparable between stages IIIA and IIA (13.0% vs 13.6%) and between stages IIIB and IIB (18.4% vs 22.0%), respectively. These risk patterns persisted in cause-specific hazards models. Conclusions and Relevance: This nationwide, population-based cohort study found that the increasing stages of the current AJCC8 staging system do not accurately reflect an increasing risk of recurrence and mortality in melanoma. The high proportion of distant recurrences suggests that hematogenous spread is a more common metastatic pathway than previously assumed, and surveillance with routine functional/cross-sectional imaging should be considered for stages IIB to IV. Future efforts should be put toward developing new tools for risk stratification and determining the survival effect of routine imaging in surveillance.

More sentinel lymph node biopsies for thin melanomas after transition to AJCC 8th edition do not increase positivity rate: A Danish population-based study of 7148 patients.

BACKGROUND: We evaluated the outcome of sentinel lymph node biopsies (SLNB) in patients with thin melanoma before and after the implementation of AJCC 8th edition (AJCC8) and identified predictors of positive sentinel lymph nodes (+SLN). METHODS: Patients diagnosed with T1 melanomas (Breslow thickness ≤1 mm) during 2016-2017 as per AJCC 7th edition (AJCC7) (n = 3414) and 2018-2019 as per AJCC8 (n = 3734) were identified in the Danish Melanoma Database. RESULTS: More SLNBs were performed in the AJCC8 cohort compared to the AJCC7 (22.2% vs. 16.2%, p < 0.001), with no significant difference in +SLN rates (4.7% vs. 6.7%, p = 0.118). In the AJCC7 + SLN subgroup, no melanomas were ulcerated, 94.6% had mitotic rate (MR) ≥ 1, 67.6% were ≥0.8 mm and 32.4% would be T1a according to AJCC8. In the AJCC8 + SLN subgroup, 10.3% were ulcerated, 74.4% had MR≥ 1, 97.4% were ≥0.8 mm and 23.1% would be T1a according to AJCC7. On multivariable analysis younger age and MR ≥ 1 were significant predictors of +SLN. CONCLUSION: More SLNBs were performed in T1 melanomas after transition to AJCC8 without an increase in +SLN rate. None of the AJCC8 T1b criteria were significant predictors of +SLN. We suggest that mitosis and younger age should be considered as indications for SLNB in thin melanoma.